DESCRIPTION: (Adapted from the applicant's abstract and Specific Aims.) The broad objectives of this application are to gain deeper insight into the mechanisms operating during the carotid body's (cb) chemotransduction of hypoxia, hypercapnia, and acidosis into increased neural activity recordable in the carotid sinus nerve. On the assumption that (a) the essential chemotransductive unit consists of the Type I cell and the apposed neuron, (b) that hypoxia depolarizes the Type I cell provoking the release of neuroagent(s) which bind to a receptor(s) on the apposed neuron, and (c) this initiates processes responsible for the recordable action potentials in the carotid sinus nerve, two questions can be asked: (1) How is the Type I cell depolarized so as to release the neuroagents? (2) What are the essential excitatory and inhibitory neuroagents in the cat and how are they managed? This application addresses the second question.Five areas of research are proposed, each containing focused hypotheses to be tested: (1) Analyze the venous effluent from the in situ cat carotid body for neurotransmitters (Are those released during hypercapnia the same as those released during hypoxia?); (2) Identify the cb's excitatory and inhibitory neurotransmitters and their pharmacological interaction (Does the cb respond more to hypoxia in the presence of an M2 receptor blocker?); (3) Determine the presence and location of specific neurotransmitter receptors (Is there a neuronal nicotinic receptor on the dendrite apposed Type I cell?); (4) determine the effect of cholinergic agonists and dopamine on membrane potential and potassium channels of the Type I cells (What does ACh do to the calcium-activated potassium current?); (5) Repeat the studies of (2) in the rabbit which responds differently from the cat. Techniques include neural recording, HPLC analysis, immunocytochemistry, and patch clamping cultured Type I cells. Better knowledge of how the cb works could perhaps allow the creation of an agent to temporarily block input from the cb.